CRF01_AE-Specific Neutralizing Activity Observed in Plasma Derived from HIV-1-Infected Thai Patients Residing in Northern Thailand: Comparison of Neutralizing Breadth and Potency between Plasma Derived from Rapid and Slow Progressors

Sompong Sapsutthipas,Masanori Kameoka,Naho Tsuchiya,Koya Ariyoshi,Naokazu Takeda,Panita Pathipavanich,Pathom Sawanpanyalert,Panasda Isarangkura-Na-Ayuthaya

doi:10.1371/journal.pone.0053920

Abstract

BackgroundDevelopment of a protective vaccine against human immunodeficiency virus type 1 (HIV-1) is an important subject in the field of medical sciences; however, it has not yet been achieved. Potent and broadly neutralizing antibodies are found in the plasma of some HIV-1-infected patients, whereas such antibody responses have failed to be induced by currently used vaccine antigens. In order to develop effective vaccine antigens, it is important to reveal the molecular mechanism of how strong humoral immune responses are induced in infected patients. As part of such studies, we examined the correlation between the anti-HIV-1 neutralizing antibody response and disease progression.Methodology/Principal FindingsWe evaluated the anti-HIV-1 neutralizing activity of plasma derived from 33 rapid and 34 slow progressors residing in northern Thailand. The level of neutralizing activity varied considerably among plasmas, and no statistically significant differences in the potency and breadth of neutralizing activities were observed overall between plasma derived from rapid and slow progressors; however, plasma of 4 slow progressors showed neutralizing activity against all target viruses, whereas none of the plasma of rapid progressors showed such neutralizing activity. In addition, 21% and 9% of plasmas derived from slow and rapid progressors inhibited the replication of more than 80% of CRF01_AE Env-recombinant viruses tested, respectively. Neutralization of subtype B and C Env-recombinant viruses by the selected plasma was also examined; however, these plasma samples inhibited the replication of only a few viruses tested.Conclusions/SignificanceAlthough no statistically significant differences were observed in the potency and breadth of anti-HIV-1 neutralizing activities between plasma derived from rapid and slow progressors, several plasma samples derived from slow progressors neutralized CRF01_AE Env-recombinant viruses more frequently than those from rapid progressors. In addition, plasma derived from HIV-1-infected Thai patients showed CRF01_AE-specific neutralizing activity.

Highlights

More than 30 million individuals are infected with human immunodeficiency virus type 1 (HIV-1) worldwide, and 2.5 million new infections have been estimated to occur yearly; an HIV-1 vaccine is urgently required
As part of studies to reveal the molecular mechanism of how strong humoral immune responses are elicited in HIV-1-infected patients, we performed a comparative study on the neutralizing activity of plasma derived from rapid and slow progressors residing in northern Thailand, using previously established high throughput neutralization tests with CRF01_AE Env-recombinant, luciferase reporter viruses [11,12]
We performed a comparative study on the antiHIV-1 neutralizing activity of plasma samples derived from rapid and slow progressors residing in northern Thailand

Summary

Introduction

More than 30 million individuals are infected with human immunodeficiency virus type 1 (HIV-1) worldwide, and 2.5 million new infections have been estimated to occur yearly; an HIV-1 vaccine is urgently required. Neutralizing antibodies are a critical component of the protective immunity required for developing an effective HIV-1 vaccine [1]. Plasma of some HIV-1-infected patients contains potent and broadly reactive neutralizing antibodies, and human monoclonal antibodies with broad and potent neutralizing activity have been established [3,4,5,6,7,8]. Ing how such neutralizing antibodies are elicited in infected patients may provide valuable insights into developing an effective HIV-1 vaccine. As part of studies to reveal the molecular mechanism of how strong humoral immune responses are elicited in HIV-1-infected patients, we performed a comparative study on the neutralizing activity of plasma derived from rapid and slow progressors residing in northern Thailand, using previously established high throughput neutralization tests with CRF01_AE Env-recombinant, luciferase reporter viruses [11,12]

Methods

Results

Discussion